The epidemic of genital HSV-2 continues to spread in the United States. The seroprevalence of HSV-2 is now 21.78% and has increased 31% in the last 1 years. Neonatal HSV and HSV infections in HIV+ persons continue to have high morbidity and attempts at developing subunit vaccines for HSV-2 have met with partial success at best. This proposal describes a renewal of the collaborative research program on genital herpes directed by Dr. Lawrence Corey of the University of Washington. During the last funding period over 57 publications and 20 abstracts emanated from this program. The specific aims of the renewal are directed at: 1) defining the epidemiologic, virological and immunologic levels associated with the transmission/acquisition of genital HSV infection, 2) initiating studies to reduce the transmission of HSV between couples and mother to infant, 3) evaluating the role HSV plays in HIV acquisitions and progression, and 4) evaluating the role mucosal T cell responses play in HSV reactivation. The 4 proposed projects are: Project I: HSV infection in HIV Infected Individuals, Lawrence Corey, MD. PI: Project II: Prevention of HSV Morbidity in Pregnancy and Newborn, Zane Brown, MD, PI; Project III: Biology and Epidemiology of Genital HSV Acquisition, Anna Wald, MPH, PI; Project IV: Mucosal T cell responses to HSV infection, David Koelle, MD, PI. These projects are supported by 4 core subject facilities which service each of the projects and facilitate the scientific objectives of each of the projects. The 4 cores include A) Administrative Core (L. Corey), B) Statistical Core (Judith Zeh, PI). C) Laboratory Core (R. Ashley, PI) and D) Clinical Core (Anna Wald, PI). The proposed studies involve 6 clinical and 4 laboratory facilities listed below.